Dendritic cells are specialized cells of the immune system with the unique capacity for initiating primary and secondary T and B lymphocyte responses. Characterized as professional antigen presenting cells (APCs), dendritic cells express MHC and costimulatory molecules essential in priming naïve T lymphocytes. This unique property of dendritic cells, also termed “nature's adjuvant”, has led to a great interest in their possible role of autoimmune diseases as well as their potential for exploitation in immunotherapy of various diseases.
Recent advances in culturing of dendritic cells has greatly increased our understanding of this complex type of cells. There are several type of dendritic cells that are distinguished by their lineage, location in tissues, phenotype, and function. The dendritic cells type that most prominently associates with T lymphocytes for the initiation of immune responses is of bone marrow origin. Bone marrow-derived dendritic cells can be further segregated into 1) thymic dendritic cells, which are of lymphoid origin and appear to be involved specifically in deletion of maturing T lymphocytes, 2) Langerhans cells, which are of myeloid lineage and have specialized APC function in the skin, and 3) myeloid lineage-derived dendritic cells found particularly in the blood, spleen and lymph nodes.
The hallmarks of myeloid lineage-derived dendritic cells (including Langerhans cells) are the following: 1) capacity for antigen uptake, and processing for presentation, 2) capacity for selective migration in tissues, and 3) capacity for direct stimulation of T lymphocytes (both naïve and primed).
Despite the recent advances in characterization of dendritic cells, very little is known regarding dendritic cell specific receptors or molecules. There are numerous dendritic cell-associated molecules that are shared with other myeloid and non-myeloid cells, however, very limited reagents are available which are specific to dendritic cells. Reagents, in particular antibodies, which react specifically or preferentially with dendritic cells have great potential as targeting agents to induce potent immune responses to tumor or infectious disease antigens. These cell-specific targeting agents could also be engineered to deliver toxins to eliminate potent APCs (e.g., dendritic cells) in bone marrow and organ transplantations or other autoimmune disorders.
Accordingly, dendritic cell-specific binding agents would be of great therapeutic and diagnostic value.